The specific aims of this research are to analyze at both the light (LM) and electron microscopic (EM) levels the structure and nature of the dental and periodontal innervation of rats and monkeys. These studies will involve: 1) tissue in which select populations of dental and periodontal nerve fibers have been labeled experimentally by the anterograde transport of horseradish peroxidase (HRP), 2) experiments to determine under what conditions, if any, the vesicles found in some dental nerve terminals can be released and if there exists within the dental nerve terminals a mechanism for the retrievel of membrane that might be compensatory for exocytosis and, 3) tissue in which substance P (SP)-containing primary sensory neurons in the dental pulp have been labeled by immunocytochemical procedures. In the first series of experiments, the tracer HRP will be injected into either the trigeminal or superior cervical ganglia or rats and monkeys. The enzyme will be endocytosed by the ganglion cell bodies and transported intraaxonally to tooth pulp and periodontal nerve terminals. The HRP labeled nerve endings will be identified at the electron microscopic level and analyzed with reference to their respective origins, ultrastructures, numbers, modes of termination and peripheral distribution. In the second series of experiments, the significance of the vesicles found in many dental nerve terminals will be investigated. Initial experiments will determine if the vesicles can be released from the dental nerve terminals by antidromic or orthodromic-stimulation. In subsequent experiments, ultrastructural documentation of HRP endocytosis by intact dental nerve terminals in the stimulated or non stimulated state, will be used to determine if these fibers possess a mechanism for the internalization of surface membrane from the axon terminal. Finally, substance-P-containing fibers in the dental pulp will be examined at both the LM and EM levels with respect to their structure, distribution and mode of termination, also it will be determined if these fibers release SP from their terminals following antidromic or orthodromic stimulation. The results of the present study will increase our understanding of the nature and sources of dental and periodontal innervation. The long range goal is to correlate this information with additional functional studies in order to increase our understanding of the peripheral mechanisms of dental and periodontal sensation and their role in normal physiological and pathological processes.